Effect of Gingivitis on Azithromycin Concentrations in Gingival Crevicular Fluid

Abstract

Aim Macrolide antibiotics yield high concentrations in inflamed tissue, suggesting that their levels in gingival crevicular fluid (GCF) could be increased at gingivitis sites. However, the increased volume of GCF associated with gingivitis could potentially dilute macrolides. To determine whether these assumptions are correct, the bioavailability of systemically-administered azithromycin was compared in GCF from healthy and gingivitis sites. Materials and methods Experimental gingivitis was induced in one maxillary posterior sextant in nine healthy subjects. Contralateral healthy sextants served as controls. Subjects ingested 500 mg of azithromycin followed by a 250 mg dose 24 hours later. Four hours after the second dose, plaque was removed from experimental sites. GCF was collected from 8 surfaces in both the experimental and control sextants and pooled separately. GCF samples were subsequently collected on the 2nd, 3rd, 8th and 15th days and azithromycin content was determined by agar diffusion bioassay. Results On days 2 and 3, the pooled GCF volume at experimental sites was significantly higher than at control sites (P <0.01) and the total azithromycin mass in 30 second GCF samples pooled from experimental sites was significantly higher than at control sites (P < 0.02). However, there were no significant differences in azithromycin concentration between the experimental and control pools at any point. Concentrations exceeded 7.3 μg/ml on day 2 and 2.5 μg/ml on day 15. Conclusions Azithromycin concentrations are similar in GCF from gingivitis sites and healthy sites, suggesting that the processes that regulate GCF azithromycin concentration can compensate for local inflammatory changes.

Azithromycin Enhances Phagocytic Killing of Aggregatibacter actinomycetemcomitans Y4 by Human Neutrophils

“…A recent pharmacokinetic study found that AZM concentrations in gingival crevicular fluid can approach 10 μg/mL and exceed 4 μg/mL for more than a week after the final oral dose. 16 The study suggested that a standard regimen of AZM (initial dose of 500 mg, followed by 250 mg every 24 hours for the next 4 days) provides tissue levels in excess of the 2-μg/mL concentration used in the current study for at least 15 days. Counts of A. actinomycetemcomitans , 35,36 P. gingivalis , 35 and neutrophils 37,38 recovered from AgP sites suggest that MOI ranges from 14:1 at a typical site to 167:1 at sites with the highest levels of A. actinomycetemcomitans , and up to 150:1 at sites with the highest levels of P. gingivalis .…”

“…18 Bacteria were washed and opsonized at 37°C for 30 minutes in HBSS containing 20% human serum pooled from ≈200 donors. ¶ Neutrophils were loaded for 15 minutes at 37°C with either 2 μg/mL AZM # (the lowest concentration typically measured in gingival crevicular fluid during a 2-week period after systemic administration 16 ) or 16 μg/mL AMX. # Broth dilution assays were used to confirm that these concentrations correspond to four times the minimum inhibitory concentration (MIC) for A. actinomycetemcomitans strain Y4.…”

“…13,14 It is active against A. actinomycetemcomitans, and its therapeutic levels in gingival crevicular fluid are sustained for at least 14 days after the last oral dose. 15,16 Previous studies have shown that accumulation of AZM inside human gingival epithelial cells facilitates killing of intraepithelial A. actinomycetemcomitans . 13 When active transport of AZM was inhibited by a competitive inhibitor, there was a significant decrease in the killing of intraepithelial bacteria.…”

Azithromycin Kills Invasive Aggregatibacter actinomycetemcomitans in Gingival Epithelial Cells

“…Thus, it appears that moxifloxacin, doxycycline, and AZM can kill intraepithelial A. actinomycetemcomitans at concentrations near those attainable in GCF. One advantage of AZM is that its therapeutic levels in GCF are sustained for an unusually long time (Ն14 days after the last oral dose) (34).…”

Validation of Antibiotic Efficacy on In Vitro Subgingival Biofilms

“…Administration of 100 mg doxycycline hyclate resulted in approximately 2 μg/mL in GCF 2 hours after a single‐dose administration 7 . Administration of 500 mg azithromycin, followed by 250 mg 24 hours later, resulted in 7.5 and 2.5 μg/mL in GCF after 2 and 15 days, respectively 8 …”